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Experimental and clinical research has reported beneficial effects of polyphenol intake on high prevalent diseases such as type 2 diabetes and obesity. These phytochemicals are ligands of taste 2 receptors (T2Rs) that have been recently located in a variety of organs and extra-oral tissues. Therefore, the interaction between polyphenol and T2Rs in brain structures can play a direct effect on appetite/satiety regulation and food intake. T2Rs are also expressed along the digestive tract, and their interaction with polyphenols can induce the release of gastrointestinal hormones (e.g., ghrelin, GLP-1, CCK) influencing appetite, gastrointestinal functionally, and glycemia control. Intestinal microbiota can also influence on network effects of polyphenols-T2Rs interaction and vice versa, impacting innate immune responses and consequently on gut functionally. Furthermore, polyphenols binding to T2Rs present important effects on adipose tissue metabolism. Interestingly, T2R polymorphism could, at least partially, explain the inter-individual variability of the effects of polyphenols on glucose and body weight homeostasis. Together, these factors can contribute to understand the beneficial effects of polyphenol-rich diets but also might aid in identifying new pharmacological pathway targets for the treatment of diabetes and obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Bitter taste receptors (TAS2Rs) and their downstream signaling pathways are expressed not only in the oral tissues but also in extraoral tissues. Emerging data has demonstrated the beneficial effect of ghrelin in neurodegenerative diseases. Gaining more insight into the interaction between TAS2Rs and gut hormones may expand their therapeutic applications. Herein, we aimed to assess the possible effect of TAS2R activation by denatonium benzoate (DB) in modulating functional and neurobiochemical alterations in a model of Parkinson's disease (PD)., Main Methods: PD model was induced by daily injection of rotenone (2 mg/kg). Rats received DB (5 mg/kg), atenolol (10 mg/kg), or both concomitantly with rotenone, daily for 28 days. Evaluation of the motor abnormalities and histological examination of brain tissues were conducted. In addition, striatal dopamine contents, immunohistochemical expression of tyrosine hydroxylase, plasma ghrelin level, and biochemical analysis of markers of inflammation and oxidative stress were assessed., Key Findings: Treatment with DB increased serum levels of ghrelin and striatal dopamine contents with consequent amelioration of oxidative stress and attenuation of inflammatory cytokines. Moreover, DB treatment significantly ameliorated motor disturbance and histological abnormalities compared to untreated rats. Atenolol inhibited ghrelin release and abolished the positive effect of DB suggesting the involvement of ghrelin on such effects., Significance: The current study suggests that TAS2Rs agonists are promising candidates for ameliorating rotenone-induced PD pathology in rats, an action that could be linked to the enhancement of ghrelin release with consequent antioxidant and anti-inflammatory activities., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C β2 (PLCβ2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCβ2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gβγ inhibitor Gallein, or a PLCβ2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Taste is a fundamental mechanism whereby compounds are detected orally, yet it is highly variable among individuals. The variability in taste that is attributable to genetics is not well-characterized despite its potential role in food selection, and therefore, eating habits that contribute to risk of overweight and obesity. In order to implicate measures of taste function and preference as potentially deterministic factors in adverse eating behaviors that lead to obesity, it must be shown that a relationship exists between genetic variation in taste receptor genes and psychophysical measures of taste in the absence high body mass index. The primary objective of this pilot study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in taste receptor genes and 3 different psychophysical measures of taste in healthy young adults. Sweet, salt, umami, fat, sour, and bitter taste receptor gene SNPs were genotyped in 49 participants (ages 24.6 ± 0.6 years) who completed testing to determine oral detection threshold (DT), suprathreshold sensitivity (ST) and taste preference (PR). A simultaneous association test was conducted between each SNP and the 3 taste outcomes (DT, ST, and PR). Twelve SNPs were associated with at least one of the 3 taste outcomes. Associations were observed between SNPs in taste receptor genes and psychophysical measures of sweet, fat, umami, and salt taste. These results suggest that differences in interindividual psychophysical measures of tastes, namely DT, ST, and PR, may be partially attributed to genetic variation in taste receptor genes. Future studies are warranted to investigate if these findings have consequences for habitual dietary intake of foods that elicit these tastes., (Copyright © 2020. Published by Elsevier Inc.)

Polyphenols are phytochemical compounds found mostly in plants with several biological properties. Many of the benefits attributed to fruits and vegetables have been linked to their content in these molecules. As a result, the last decade has witnessed an increase in polyphenol-derived compounds claiming diverse therapeutic properties. Although the mechanism of action of such compounds is yet to be fully disclosed, one of the components that recently has been proposed to participate significantly in the health properties of polyphenols is the type 2 taste receptors (T2Rs). These receptors are responsible for the detection of bitter taste and represent the first line of defence against potentially harmful components in food. The recent discovery of extra-oral T2Rs in several metabolically active tissues has generated intense interest in the potential health impact. Given that most phenolic molecules taste bitter, exploring the T2Rs as a putative pharmacological target for the development of plant-based drug therapies is a promising field of research. Some T2Rs are involved in the control of cilia beat frequency and smooth muscle relaxation in the air tract together with leukocyte homeostasis, important events disrupted in the high prevalence of respiratory diseases. Furthermore, T2Rs are involved in nutrient-gut interactions to modulate gut hormones that influence gastrointestinal motility, appetite and glycemia. Thus, this commentary focuses on the latest novelty advances in relation to the peripheral expression of T2Rs, and polyphenols and T2Rs relationship from a therapeutic point of view., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The choroid plexus (CP) epithelial cells establish an important blood-brain interface, the blood-cerebrospinal fluid barrier (BCSFB), which constitutes a complementary gateway to the blood-brain-barrier for the entrance of several molecules into the central nervous system (CNS). However, the mechanisms that operate at the BCSFB to regulate the molecular traffic are still poorly understood. The taste signalling machinery, present in many extra-oral tissues, is involved in the chemical sensing of the composition of body fluids. We have identified this pathway in rat CP and hypothesised that it could also be present in the human BCSFB. In this study, we characterised the bitter taste receptors (TAS2Rs) expression profiling in human CP by combining data retrieved from available databases of the human CP transcriptome with its expression analysis in a human CP cell line and immunohistochemistry of human CP sections from men and women. TAS2R4, 5, 14 and 39 expression was confirmed in human CP tissue by immunohistochemistry and in HIBCPP cells by RT-PCR, immunofluorescence and Western blot. Moreover, the presence of downstream effector proteins GNAT3, PLCβ2 and TRPM5 was also detected in HIBCPP cells. Then, we demonstrated that HIBCPP cells respond to chloramphenicol via TAS2R39 and to quercetin via TAS2R14. Our findings support an active role of TAS2Rs at the human BCSFB, as surveyors of the bloodstream and CSF compositions. These findings open new avenues for studies on the uptake of relevant compounds for targeted therapies of the CNS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The regulation of transport mechanisms at brain barriers must be thoroughly understood, so that novel strategies for improving drug delivery to the brain can be designed. The blood-cerebrospinal fluid barrier (BCSFB) established by the choroid plexus (CP) epithelial cells has been poorly studied in this regard despite its relevance for the protection of the central nervous system (CNS). This study assessed the role of bitter taste receptors (TAS2Rs), TAS2R14 and TAS2R39, in the transport of resveratrol across CP epithelial cells using an in vitro model of the human BCSFB. Both receptors are expressed in human CP cells and known to bind resveratrol. First, Ca 2+ imaging assays demonstrated that resveratrol specifically activates the TAS2R14 receptor, but not TAS2R39, in these human CP epithelial cells. Then, we proceeded with permeation studies that showed resveratrol can cross the human BCSFB, from the blood to the CSF side and that TAS2R14 knockdown decreased the transport of resveratrol across these cells. Conversely, inhibition of efflux transporters ABCC1, ABCC4 or ABCG2 also restrained the transport of resveratrol across these cells. Interestingly, resveratrol upregulated the expression of ABCG2 located at the apical membrane of the cells via TAS2R14, whereas ABCC1 and ABCC4 at the basolateral membrane of the cells were not affected. Altogether, our study demonstrates that the BCSFB is a gateway for resveratrol entrance into the CNS and that the receptor TAS2R14 regulates its transport by regulating the action of efflux transporters at CP epithelial cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bitter taste receptors (Tas2rs), the members of the G-protein-coupled receptors, mediate the bitter taste and express in extra-oral tissues. Previous studies have shown that Tas2r mRNAs are expressed in the whole heart and cultured cardiomyocytes of neonatal rats. This study aimed to determine the expression of Tas2rs and their function in the adult rat hearts by using RT-qPCR techniques, Langendorff-perfused isolated hearts, and isolated sinoatrial (SA) nodes. The data presented here revealed the mRNA expression of Tas2rs and their coupled G-protein subunits in the SA node and left ventricle of adult rat hearts. Tas2r agonists, quinine and chloroquine, decreased the heart rate and increased the RR interval and QRS duration in Langendorff-perfused isolated rat hearts; they reduced the spontaneous beating rate of isolated SA nodes with pEC 50 values of 4.907 ± 0.045 and 4.968 ± 0.030, respectively. The blockade of Tas2r108 with abscisic acid, the inhibition of phosphodiesterases (PDEs) with 3-isobutyl-1-methylxanthine (IBMX), or the selective inhibition of PDE3 and PDE4 with a cocktail of cilostamide and rolipram, attenuated the negative chronotropic effects of quinine and chloroquine on the SA node. Furthermore, quinine and chloroquine suppressed the tachycardia effect of isoprenaline on the SA node and shifted the concentration-response curve of isoprenaline rightward. In summary, we provided a few lines of evidence that Tas2r agonists, quinine and chloroquine, decreased the heart rate by prolonging ventricular depolarization, and by attenuating the SA node pace in a PDE-dependent manner; they can counteract with β-adrenergic receptor activation and eliminate isoprenaline-induced tachycardia., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, molecular dynamics simulations, from all atom and coarse grained to hybrid methods bridging the two scales, have provided exciting functional insights into class F (Frizzled and Taste2) GPCRs (about 40 members in humans). Findings include: (i) The activation of one member of the Frizzled receptors (FZD4) involves a bending of transmembrane helix TM7 far larger than that in class A GPCRs. (ii) The affinity of an anticancer drug targeting another member (Smoothened receptor) decreases in a specific drug-resistant variant, because the mutation ultimately disrupts the binding cavity and affects TM6. (iii) A novel two-state recognition mechanism explains the very large agonist diversity for at least one member of the Taste2 GPCRs, hTAS2R46., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The choroid plexus (CP) located in brain ventricles, by forming the interface between the blood and the cerebrospinal fluid (CSF) is in a privileged position to monitor the composition of these body fluids. Yet, the mechanisms involved in this surveillance system remain to be identified. The taste transduction pathway senses some types of molecules, thereby evaluating the chemical content of fluids, not only in the oral cavity but also in other tissues throughout the body, such as some cell types of the airways, the gastrointestinal tract, testis and skin. Therefore, we hypothesized that the taste transduction pathway could also be operating in the CP to assess the composition of the CSF. We found transcripts for some taste receptors (Tas1r1, Tas1r2, Tas1r3, Tas2r109 and Tas2r144) and for downstream signaling molecules (α-Gustducin, Plcβ2, ItpR3 and TrpM5) that encode this pathway, and confirmed the expression of the corresponding proteins in Wistar rat CP explants and in the CP epithelial cells (CPEC). The functionality of the T2R receptor expressed in CP cells was assessed by calcium imaging, of CPEC stimulated with the bitter compound D-Salicin, which elicited a rise in the intracellular Ca(2+). This effect was diminished in the presence of the bitter receptor blocker Probenecid. In summary, we described the expression of the taste-related components involved in the transduction signaling cascade in CP. Taken together, our results suggest that the taste transduction pathway in CPEC makes use of T2R receptors in the chemical surveillance of the CSF composition, in particular to sense bitter noxious compounds., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Taste perception and food preferences are influenced by a variety of factors, including personality characteristics. The aims of this study were to examine the role of personality characteristics, such as alexithymia (a personality construct characterized by inability to identify, describe, and work with one's own feelings), in: 1) taste responses to the bitter genetic taste-marker PROP and 2) food liking. We studied 649 healthy subjects residing in six genetically-isolated villages of Northeast Italy. Data on PROP taste responsiveness, food liking, personality characteristics and TAS2R28 genotypes were collected. Results showed that PROP non-tasters had higher alexithymia scores than PROP tasters. Moreover, the presence of alexithymia in heterozygous individuals for the rs1726886 polymorphism of the TAS2R38 gene was associated with a reduction in the perceived intensity of PROP. Finally, higher alexithymia scores were associated with liking of alcohol, sweets and fats/meats whereas lower alexithymia scores were related to liking of vegetables, condiments and strong cheeses, Measures of temperament, character, anxiety and depression were also related to food liking. Our findings suggest that: 1) alexithymia, in addition to the TAS2R38 polymorphism, may play a role in responsiveness to the aversive and bitter taste of PROP; and 2) alexithymia, in combination with other personality traits, may provide important insights for better understanding food liking., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To date, the majority of research exploring associations with genetic variability in bitter taste receptors has understandably focused on compounds and foods that are predominantly or solely perceived as bitter. However, other chemosensory stimuli are also known to elicit bitterness as a secondary sensation. Here we investigated whether TAS2R variation explains individual differences in bitterness elicited by chemesthetic stimuli, including capsaicin, piperine and ethanol. We confirmed that capsaicin, piperine and ethanol elicit bitterness in addition to burning/stinging sensations. Variability in perceived bitterness of capsaicin and ethanol were significantly associated with TAS2R38 and TAS2R3/4/5 diplotypes. For TAS2R38, PAV homozygotes perceived greater bitterness from capsaicin and ethanol presented on circumvallate papillae, compared to heterozygotes and AVI homozygotes. For TAS2R3/4/5, CCCAGT homozygotes rated the greatest bitterness, compared to heterozygotes and TTGGAG homozygotes, for both ethanol and capsaicin when presented on circumvallate papillae. Additional work is needed to determine how these and other chemesthetic stimuli differ in bitterness perception across concentrations and presentation methods. Furthermore, it would be beneficial to determine which TAS2R receptors are activated in vitro by chemesthetic compounds., (Copyright © 2016. Published by Elsevier Inc.)

Our previous studies revealed that berberine-mediated GLP-1 secretion was a possible mechanism for berberine exerting good effects on hyperglycemia. This study was designed to ascertain whether berberine-induced secretion of GLP-1 was related with activation of bitter taste receptors expressed in gastrointestinal tract. Western blotting results showed that TAS2R38, a subtype of bitter taste receptor, was expressed on human enteroendocrine NCI-H716 cells. GLP-1 secretion induced by berberine from NCI-H716 cells was inhibited by incubation with anti-TAS2R38 antibody. We further performed gene silencing using siRNA to knockdown TAS2R38 from NCI-H716 cells, which showed that siRNA knockdown of the TAS2R38 reduced berberine-mediated GLP-1 secretion. We adopted inhibitors of PLC and TRPM5 known to be involved in bitter taste transduction to investigate the underlying pathways mediated in berberine-induced GLP-1 secretion. It was found that PLC inhibitor U73122 inhibited berberine-induced GLP-1 release in NCI-H716 cells, while TRPM5 blocker quinine failed to attenuate berberine-induced secretion of GLP-1. The present results demonstrated that berberine stimulated GLP-1 secretion via activation of gut-expressed bitter taste receptors in a PLC-dependent manner. Because berberine was found to be a ligand of bitter taste receptor, the results of present study may provide an explanation for some bitter taste substance obtain hypoglycemic effect., (Copyright © 2015 Elsevier Inc. All rights reserved.)

PROP responsiveness is associated with TAS2R38 haplotypes and fungiform papilla density. Recently, we showed that a polymorphism in the gene coding for the salivary trophic factor, gustin (CA6), affects PROP sensitivity by acting on cell growth and fungiform papillae maintenance, in a genetically homogeneous cohort. Since population homogeneity can lead to over estimation of gene effects, the primary aim of the present work was to confirm gustin's role in PROP bitterness intensity and fungiform papillae density in a genetically diverse population. Eighty subjects were genotyped for both genes by PCR techniques. PROP responsiveness was assessed by a filter paper method and fungiform papilla density was determined in each subject. As expected, PROP bitterness ratings were lower in individuals with the AVI/AVI diplotype of TAS2R38 than in individuals with PAV/PAV and PAV/AVI diplotypes. However, no differences in PROP bitterness among genotypes of the gustin gene, and no differences in the density of fungiform papillae related to TAS2R38 diplotype were found. In contrast, the density of fungiform papillae decreased as the number of minor (G) alleles at the gustin locus increased. In addition, the distribution of TAS2R38 genotypes within each gustin genotype group showed that the occurrence of recessive alleles at both loci was infrequent in the present sample compared to other populations. These findings confirm that papillae density is associated with gustin gene polymorphism, rs2274333 (A/G), in an ancestrally heterogeneous population, and suggest that variations in the frequency of allele combinations for these two genes could provide a salient explanation for discrepant findings for gustin gene effects across populations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The PROP bitter-taste phenotype is a marker for food preferences and eating behavior, and may associate with differences in body weight in children. Previous work has shown that PROP status in combination with eating attitudes are better predictors of weight status in preadolescents, than either factor alone. However, no studies have examined the role of PROP phenotypes in body weight change in children over time. The primary objective of this study was to investigate current weight status and change in weight status in children from preschool (baseline) to preadolescence as a function of eating attitudes and PROP phenotype. Other measures included self-reported food intakes and physical activity by activity monitor. Seventy-three lean (BMI percentile=57.7±3.2%) children with mean age=10.3±0.5yrs, participated in the follow up. There were no group differences in energy intake, current BMI-percentile or change in BMI percentile from baseline by PROP phenotype in either boys or girls. However, there was a trend for non-taster girls to show a downward shift in BMI-percentile at follow up. Hierarchical regression analysis revealed that baseline BMI percentile and physical activity energy expenditure were the strongest predictors of current weight (28.5% variance),followed by child restraint, the taster×gender interaction, and the maternal BMI×maternal emotional eating interaction, accounting for 7.1%, 6.0% and 4.8% of variance in the model, respectively. These findings suggest that PROP status and eating attitudes are modest predictors of weight status in preadolescent children., (Copyright © 2013. Published by Elsevier Inc.)

The objective of this study was to determine whether humans could detect long-chain fatty acids when these lipid molecules are delivered to the oral cavity by edible taste strips. For suprathreshold studies, up to 1.7 μmol of stearic acid or linoleic acid was incorporated into 0.03 mm thick, one-inch square taste strips. Normalized taste intensity values for stearic acid were in the barely detectable range, with values equal to, or slightly above control strips. One-third of test subjects described the taste quality as oily/fatty/waxy. Approximately 75% of test subjects could detect the presence of linoleic acid when this fatty acid was incorporated into dissolvable strips. Normalized taste intensity values for linoleic acid were in the weak to moderate range. The most commonly reported taste quality responses for linoleic acid were fatty/oily/waxy, or bitter. When nasal airflow was obstructed, the perceived taste intensity of linoleic acid decreased by approximately 40%. Taste intensity values and taste quality responses for linoleic acid were then compared among tasters and non-tasters of 6-n-propylthiouracil (PROP). Individuals who could detect the bitter taste of PROP reported higher taste intensity values for linoleic acid compared with PROP non-tasters. However, taste quality responses for linoleic acid were similar among both PROP tasters and PROP non-tasters. These results indicate that humans can detect long-chain fatty acids by both olfactory and non-olfactory pathways when these hydrophobic molecules are delivered to the oral cavity by means of edible taste strips. These studies further show that genetic variation in taste sensitivity to PROP affects chemosensory responses to the cis-unsaturated fatty acid (linoleic acid) in the oral cavity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The PROP taste phenotype varies greatly among individuals, influencing eating behavior and therefore may play a role in body composition. This variation is associated with polymorphisms in the bitter receptor gene TAS2R38 and the taste-bud trophic factor gustin gene. The aim of this study was to examine the relationship between TAS2R38 haplotypes and the gustin gene polymorphism rs2274333 in modulating PROP taste phenotype. PROP phenotype was determined in seventy-six volunteers (29 males, 47 females, age 25±3 y) by scaling methods and threshold measurements. TAS2R38 and gustin gene genotyping was performed using PCR techniques. The lowest responsiveness in PROP nontasters is strongly associated with the AVI nontasting TAS2R38 variant and the highest responsiveness in supertasters is strongly associated to allele A and genotype AA of the gustin gene. These data support the hypothesis that the greater sensitivity of supertasters could be mediated by a greater taste-bud density. Polymorphisms in TAS2R38 and gustin gene, together, accounted for up to 60% of the phenotypic variance in PROP bitterness and to 40% in threshold values. These data, suggest that other unidentified factors may be more relevant for detecting low concentrations of PROP. Moreover, the presence of the PAV variant receptor may be important for detecting high concentrations of PROP, whereas the presence of allele A in gustin polymorphism may be relevant for perceiving low concentrations. These data show how the combination of the TAS2R38 and gustin gene genotypes modulate PROP phenotype, providing an additional tool for the evaluation of human eating behavior and nutritional status., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Taste receptor cells are primary sensory receptors utilized by the nervous system to detect the presence of gustatory stimuli in the oral cavity. These cells are particularly heterogeneous and may be divided into various subtypes based on morphological, histochemical, or physiological criteria. One example is the heterogeneous expression of neuropeptides, such as cholecystokinin and vasoactive intestinal polypeptide. These peptides are hypothesized to participate in the transduction processes. To pursue examination of this hypothesis, this study explored the relationship of peptide expression with two important and mostly non-overlapping transductive elements--the taste-specific G protein gustducin, involved in bitter and sweet transduction cascades, and the seven transmembrane taste receptor T1R2, hypothesized to respond to sweet compounds. Double labeling experiments were performed on taste buds of the posterior rat tongue combining immunocytochemistry for peptide expression and in situ hybridization experiments for either gustducin or T1R2 expression. Additionally, vasoactive intestinal peptide (VIP)-expression in posterior taste receptor cells was confirmed using the technique of RT-PCR. More than half (56%) of the CCK-expressing taste receptor cells co-expressed alpha-gustducin mRNA whereas far fewer (15%) co-expressed T1R2 mRNA. A majority of VIP-expressing taste receptor cells co-expressed alpha-gustducin mRNA (60%) whereas only 19% of these cells co-expressed T1R2 mRNA. More remarkable was the observation that these two peptides displayed almost identical expression patterns with these signal transduction molecules, suggesting that peptides are not randomly expressed with relation to signal transduction molecules. This observation supports the hypothesis that peptides may play roles in transduction. Further physiological exploration will be required to elucidate the nature of these roles.

Taste receptors are thought to couple to the G protein Galpha-gustducin to initiate signal transduction cascades leading to taste perception. To further characterize the G protein-coupling selectivity of these receptors, we expressed them in HEK293 cells and monitored the modulation of different signaling pathways upon stimulation. We found that the bitter compound cycloheximide induces phosphorylation of extracellular signal-regulated kinases1 and 2 (ERK 1/2) and inhibits cAMP accumulation in HEK293 cells expressing the mouse bitter T2R(5) receptor. These effects are totally abolished upon treatment with pertussis toxin. On the other hand, sweeteners and monosodium glutamate induce phosphorylation of ERK1/2 and inhibit cAMP accumulation in HEK293 cells expressing the human sweet T1R(2)/T1R(3) receptor and the human umami T1R(1)/T1R(3) receptor, respectively. The effects of these taste modalities are also prevented by treatment with pertussis toxin. Collectively, our results show that taste receptors can functionally couple to Galpha(i/o) proteins to transmit intracellular signals.